Sue Biggins, genetics and biology researcher

Discovering how cells get the right chromosomes

As a newly minted researcher a decade ago, Dr. Sue Biggins chose the Fred Hutch because of what it isn’t: It isn’t about playing it safe or working alone. It isn’t about empire building. It’s not full of policies and politics to trip over. It’s all about having the freedom, she said, to do the best, most unconventional science possible.

“Definitely more home runs are hit here because there’s an unspoken expectation that you should do something big, stuff that’s really going to be a game-changer,” Biggins said. “Good fundamental science is inherently risky.”

Before she became a researcher, Biggins thought the mechanics of cell division were completely understood. It didn’t take her long to figure out that many questions remained, and she sought to answer some of them. In the Hutch’s Basic Sciences Division, she recently made an important contribution to the study of cell division by figuring out how specialized “cellular machines” known as kinetochores allow cells to separate and distribute their chromosomes accurately.

For decades, researchers have tried and failed to isolate or assemble whole, functioning kinetochores to better understand how they help chromosomes separate and end up in the right daughter cell. If this goes awry, entire chromosomes are gained or lost, a hallmark of most cancer tumors, hereditary birth defects and miscarriages.

Biggins’ team, stepping away from genetic methods and borrowing from biochemists’ playbook, succeeded in separating the kinetochores from dividing yeast cells and studying them in test tubes for the first time. During cell division, kinetochores act like handles on chromosomes and are under tremendous pressure as fibers pull on these handles to move the chromosomes within the dividing cell. If chromosomes fall off in the midst of this process, they don’t end up in the daughter cell. Biggins and colleagues found the harder the kinetochores are pulled, the harder they attach, like a finger trap toy. This counterintuitive characteristic explains why the process works correctly so often.

What’s true in yeast is also true in human cells. Because kinetochores play such an important role in chromosome segregation, knowing how they work turns them into very large therapeutic targets. If research leads to drugs that disrupt kinetochores from doing their job in unhealthy cells, they would be unable to divide and propagate at all, stopping a disease such as cancer.

Biggins’ breakthrough came with help from a fellow researcher who took time teach her biochemistry methods. “I had absolutely no experience with biochemistry, but it was clear to me that for the field to progress, someone had to figure out how to pull the kinetochore out of the cell,” she said, noting that her colleague’s assistance is commonplace at the Hutch, where collegiality is prized. “I’m surrounded by unselfish colleagues willing to make other labs as successful as their own,” she said.